Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain

Lindberg, Julia; Saetre, Peter; Nishino, Seiji; Mignot, Emmanuel; Jazin, Elena

doi:10.1186/1471-2202-8-34

Cited by 6 publications

(5 citation statements)

References 56 publications

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“…The finding that OX increases gene expression and peptide levels of SP in this subregion is the first direct evidence for a close relationship between these neuropeptides. This is consistent with indirect evidence, showing that a mutation of OX2R decreases gene expression of tachykinin precursor 1 (Lindberg et al ) and that OX1R exists on SP‐containing dorsal root ganglion neurons (Colas et al ). The smaller increase in SP peptide relative to mRNA levels may reflect the difference in the timing of their measurement, with levels possibly higher shortly after OX injection.…”

Section: Discussionsupporting

confidence: 90%

“…This neuropeptide may have similar actions in the PVT, where it has been detected in perikarya and fibers (McLean, Skirboll & Pert ; Battaglia, Spreafico & Rustioni ) and NK1R has also been described (Mantyh, Hunt & Maggio ). The idea that SP in the PVT may function in close relation to OX is suggested by the finding that expression of tachykinin precursor 1, which encodes SP, is enhanced in the amygdala of dogs with a mutation of OX2R (Lindberg et al ) and that OX1R in rats is expressed on SP‐containing dorsal root ganglion neurons (Colas et al ). These studies hint at the possibility that SP may function in close relation to OX, acting in the PVT to stimulate ethanol drinking.…”

Section: Introductionmentioning

confidence: 99%

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Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus

Barson

Poon

et al. 2015

Addiction Biology

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The paraventricular nucleus of the thalamus (PVT) appears to participate in drug addiction. Recent evidence in rats shows that ethanol drinking is increased by orexin/hypocretin (OX) afferents from the hypothalamus, acting specifically in the anterior (aPVT) rather than posterior (pPVT) PVT subregion. The present study sought to identify neuropeptides transcribed within the PVT, which themselves might contribute to ethanol drinking and possibly mediate the actions of OX. We discovered that substance P (SP) in the aPVT can stimulate intermittent access ethanol drinking, similar to OX, and that SP receptor (NK1R) antagonists in this subregion reduce ethanol drinking. As with OX, this effect is site-specific, with SP in the pPVT or dorsal third ventricle having no effect on ethanol drinking, and it is behaviorally specific, with SP in the aPVT reducing the drinking of sucrose and stimulating it in the pPVT. A close relationship between SP and OX was demonstrated by a stimulatory effect of local OX injection on SP mRNA and peptide levels, specifically in the aPVT but not pPVT, and also a stimulatory effect of OX on SP expression in isolated thalamic neurons, reflecting postsynaptic actions. A functional relationship between OX and SP in the aPVT is suggested by our additional finding that ethanol drinking induced by OX is blocked by a local NK1R antagonist administered at a subthreshold dose. These results, suggesting that SP in the aPVT mediates the stimulatory effect of OX on ethanol drinking, identifies a new role for SP in the control of this behavior.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus

Barson

Poon

et al. 2015

Addiction Biology

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“…This conclusion is further supported by the recent finding that central injection of GAL or OX can stimulate endogenous expression of ENK in the PVN (Karatayev et al, 2009). In addition, one study using microarray technology has identified preproENK as one of only three molecules specifically down-regulated in the brain by a mutation of the OX 2 receptor (OX 2 R) in narcoleptic dogs (Lindberg et al, 2007). Together, these results indicate that the non-opioid peptides in the PVN, both GAL-expressing neurons and OX innervation to the nucleus, may be important regulators of local ENK, functioning through this opioid to stimulate feeding and mediating upstream the stimulatory effect of a HFD on endogenous ENK.…”

mentioning

confidence: 99%

Galanin and the orexin 2 receptor as possible regulators of enkephalin in the paraventricular nucleus of the hypothalamus: relation to dietary fat

Barson¹,

Chang²,

Poon³

et al. 2011

Neuroscience

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Recent studies show that the non-opioid peptides, galanin (GAL) and orexin (OX), are similar to the opioid enkephalin (ENK) in being stimulated by dietary fat and also in enhancing the consumption of a high-fat diet (HFD). This suggests that, when a HFD is provided, these non-opioids may stimulate the opioid system to promote excess consumption of this diet. Using single- and double-labeling immunohistochemistry, the present study sought to identify possible neuroanatomical substrates for this close relationship. Focusing on the hypothalamic paraventricular nucleus (PVN), and particularly its anterior (aPVN), middle (mPVN) and posterior (pPVN) parts, the experiments examined whether GAL itself or the receptors for GAL and OX are stimulated by a HFD in the same areas and possibly the same neurons as ENK. Compared to animals fed a standard chow diet, rats consuming a HFD exhibited an increased density of medial parvocellular neurons immunoreactive (IR) for GAL in the mPVN and aPVN and for ENK in the mPVN and pPVN, distinguishing the mPVN as an area where both peptides were affected. While showing little evidence for GAL and ENK colocalization with a chow diet, double-labeling studies in HFD-fed rats revealed significant colocalization specifically in medial parvocellular neurons of the mPVN. Immediately posterior to this site, further analyses revealed a similar relationship between the OX 2 receptor (OX2R) and ENK in HFD-treated animals. While increasing the density of neurons immunoreactive for OX2R as well as for the GAL 1 receptor but not OX 1 receptor, HFD consumption increased the colocalization only of OX2R and ENK, specifically in the medial parvocellular neurons of the pPVN. These changes in HFD-fed rats, showing GAL and OX2R to colocalize with ENK exclusively in neurons of the medial parvocellular mPVN and pPVN, respectively, suggest possible neural substrates through which the non-opioid peptides may functionally interact with ENK when exposed to a HFD.

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“…Some silico analysis implied that some important molecular signaling pathway such as IP3 pathway, IGF1R pathway, cAMP pathway may be associated with cognitive enhancement in animal models of brain disease (Jellen et al 2015 ). Based on previous research, it is suggested that TAC1 , PENK and SOCS2 might be intimately connected with the excessive daytime sleepiness not only in dogs, but also in other species, possibly including humans (Lindberg et al 2007 ). Other studies revealed that the diagnosis of narcolepsy but not CPT1B expression level was associated with abnormally and significantly low acylcarnitine levels (Miyagawa et al 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Reproducibility of quantitative real-time PCR assay in microRNA expression profiling and comparison with microarray analysis in narcolepsy

et al. 2015

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MicroRNAs (miRNAs) have been shown in the pathogenesis of human neurological disorders. The study aims to identify the involvement of miRNAs in the pathophysiology of narcolepsy. Here, we conducted three independent high-throughput analysis of miRNA (miRNA microarray) in peripheral blood from 20 narcolepsy patients who fulfilled the criteria compared to 20 healthy controls with validation experiment using quantitative real-time polymerase chain reaction (real-time PCR) panels. By analyzing 2805 miRNAs in peripheral blood with microarray we identified 128 miRNAs (105 high expression and 23 low expression) that were different in patients with narcolepsy in comparison with healthy control. Then we chose six high expression candidates and six low expression candidates of at least twofold difference and p value < 0.05 to validate the changes in three independent experiments in vitro using real-time PCR. The validation test showed that levels of hsa-mir-1267, hsa-miR-4309, hsa-miR-554, hsa-miR-1272, hsa-miR-4501, hsa-miR-182-3p were higher, whereas the level of hsa-miR-625-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-197-3p, hsa-miR-4522, hsa-miR-493-5p was lower in narcolepsy patients than healthy controls. The levels of 12 miRNAs differed significantly in peripheral blood from narcolepsy patients which suggested that alterations of miRNAs expression may be involved in the pathophysiology of narcolepsy.

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Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain

Cited by 6 publications

References 56 publications

Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus

Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus

Galanin and the orexin 2 receptor as possible regulators of enkephalin in the paraventricular nucleus of the hypothalamus: relation to dietary fat

Reproducibility of quantitative real-time PCR assay in microRNA expression profiling and comparison with microarray analysis in narcolepsy

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